EASD 2024: Incretins play all the instruments in the orchestra
Incretins are not just metabolic hormones that regulate glucose levels after eating. Their functions go beyond stimulating the release of insulin from the pancreas. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), the two main incretins, have receptors and effects in different organs, including the heart, brain, bone and kidneys. Even if they do not directly play those keys, other organs such as the liver and muscle receive signals from the same score and join the orchestra.

EASD 2024: Incretins play all the instruments in the orchestra
Incretins are not just metabolic hormones that regulate glucose levels after eating. Their functions go beyond stimulating the release of insulin from the pancreas. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), the two main incretins, have receptors and effects in different organs, including the heart, brain, bone and kidneys. Even if they do not directly play those keys, other organs such as the liver and muscle receive signals from the same score and join the orchestra.
Vironexis exits stealth with 10+ AAV-delivered immuno-oncology candidates
Vironexis Biotherapeutics Inc. has come out of stealth mode, disclosing that it has more than 10 product candidates it’s been developing over the last three years. The therapies are built on the company’s AAV-based platform, Transjoin, which is designed to have patients' livers express bispecific antibodies that bind to both CD3 on T-cells and various targets on tumor cells.
Biolexis’ oral GLP-1 agonist produces weight loss in diet-induced obesity model
Biolexis Therapeutics Inc. has announced findings from a study of its oral small-molecule GLP-1 agonist, BLX-7006, in a diet-induced obesity model in mice. In the study, BLX-7006 achieved an average weight reduction of 15% over a 28-day period.
Oruka to advance psoriasis programs into clinic next year
Oruka Therapeutics Inc. has announced plans to advance two programs for psoriasis into the clinic next year.
Other news to note for Sept. 13, 2024
Additional early-stage research and drug discovery news in brief.
JNJ-75220795 demonstrates rapid systemic absorption and elimination
Researchers from Janssen Research & Development LLC presented preclinical data for JNJ-75220795 (ARO-PNPLA3), a GalNAc-conjugated small interfering RNA (siRNA) therapeutic targeting the PNPLA3 gene, being developed for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).
Tankyrase inhibitor exerts robust preclinical antifibrotic effects
Tankyrases (TNKS) are involved in relevant cellular functions such as telomere maintenance or Wnt signaling, and their inhibition may be a potential treatment strategy for the management of hyperproliferative disorders because it counteracts profibrotic changes and blocks the synthesis of extracellular matrix proteins.
The University of Michigan patents STAT3 degradation inducers
The University of Michigan has identified proteolysis targeting chimeras (PROTACs) comprising cereblon (CRBN) ligands coupled to signal transducer and activator of transcription 3 (STAT3)-targeting moiety via linker acting as STAT3 degradation inducers.

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Conferences

Keap1-Nrf2 interaction inhibitors show activity in rat kidneys
Nephrology
Researchers from Japan Tobacco Inc. presented the discovery and preclinical characterization of novel highly potent Keap1-Nrf2 protein-protein interaction (PPI) inhibitors.
MK-4334 ameliorates cognition in Alzheimer’s disease models
Neurology/psychiatric
Neuroinflammation underlies neurodegeneration in Alzheimer’s disease (AD) and other brain disorders. The stimulation of nicotinic α7 receptors, involved in the regulation of neuroinflammation, has shown efficacy in improving memory and learning in AD models.
Partial epigenetic reprogramming to treat ischemic optic neuropathy
Science
A novel gene therapy that leads to cellular rejuvenation could restore vision after non-arteritic anterior ischemic optic neuropathy (NAION) and glaucoma. The technique is based on a reprogramming process that reverses the epigenetic DNA alterations caused by aging. Preclinical studies in glaucoma...
Discovery of AZD-4144, a potent, direct and selective NLPR3 inflammasome inhibitor
Cardiovascular
Astrazeneca plc recently provided details on the discovery of the potent, direct and selective NLPR3 inflammasome inhibitor AZD-4144 for the treatment of inflammatory diseases.

Cancer

Focusing on tumor cells brings insights into cancer neuroscience
Science
By looking at the electrical activity of tumor cells, rather than the neurons that innervate them, investigators at Baylor College of Medicine have added both basic and translational insights to the emerging field of cancer neuroscience. In their studies, which were published in Cancer Cell on...

Infection

TFF H1, H3 vaccine candidates produce protective antibodies in ferrets
Immune
TFF Pharmaceuticals Inc. has announced promising preclinical data advancing a multivalent universal influenza vaccine manufactured by its Thin Film Freezing (TFF) technology to protect against seasonal and pandemic viruses.

TC Biopharm plans preclinical studies of TCB-008 to treat mpox
Cell therapy
TC Biopharm (Holdings) plc has announced plans to begin proof-of-concept preclinical studies for its lead therapeutic, TCB-008, for the treatment of mpox.
Novel PDE4 inhibitor shows excellent hepatoprotective activity in hepatic sepsis model
Gastrointestinal
Researchers from Southern Medical University have divulged the discovery and preclinical characterization of novel PDE4 inhibitors for the treatment of hepatic sepsis. Synthesis and optimization of a series of 7-alkoxybenzofurans led to the identification of compound [I] as the lead PDE4 inhibitor,...

Neurology/psychiatric

Silo Pharma completes pre-IND meeting with FDA on SPC-15 for PTSD
Small molecule
Silo Pharma Inc. has completed a pre-IND meeting with the FDA regarding the company’s development plan for SPC-15, an intranasal prophylactic treatment for post-traumatic stress disorder (PTSD) and stress-induced anxiety disorder.
Grant supports early studies of SBT-589 for Friedreich’s ataxia
Small molecule
Stealth Biotherapeutics Inc. has been awarded the Kyle Bryant Translational Research Award from the Friedreich’s Ataxia Research Alliance (FARA) to evaluate mitochondria-targeted molecule SBT-589 in Friedreich’s ataxia (FA).
Autoimmune T cells may be beneficial for CNS injuries
Immune
Immunotherapy based on T cells is the vanguard of cancer treatments. Researchers from Washington University in St. Louis have shown that similar approaches using T cells could be applied for treating injuries of the central nervous system (CNS). They reported their findings in Nature on Sept. 4, 2024.
ML-218 reduces ischemia-reperfusion-induced abnormalities
ML-218 is an orally active, selective, and potent T-type calcium channel (Cav3.1, Cav3.2 and Cav3.3) inhibitor. Previous research has shown that ML-218 penetrates the blood-brain barrier and exerts protective effects against haloperidol-induced catalepsy, peripheral neuropathy and Parkinson’s disease.
QED-701 results in significant phenotypic improvements in models of neurodegenerative disease
Conferences
It has been previously demonstrated that the activation of spleen tyrosine kinase (SYK) contributes to processes that are central to the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD).

Endocrine/metabolic

Novo Nordisk exercises option to license Kallyope ligand for obesity
Peptide
Novo Nordisk A/S has exercised an option to license a ligand identified by Kallyope Inc. for further development, including as a potential new approach for the treatment of obesity.

Biomarkers

Alveolar macrophage IRF3 expression impacts outcome in COPD, study shows
Respiratory
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and is characterized by an abnormal inflammatory reaction of the lungs to inhaled particles, such as cigarette smoke. On the other hand, the transcription factor interferon responsive factors (IRFs)...

CCL27 and TNFRSF14 as new prognostic biomarkers of stroke progression
Cardiovascular
Researchers from University of Bristol and affiliated organizations performed studies to identify new risk factors that would predict future cardiovascular events after an incident stroke.
EAN 2024: Better diagnoses are shared dream of neurodegeneration researchers
Conferences
“Do dreams predict the future?” Abidemi Otaiku asked his audience at the 10th Congress of the European Academy of Neurology, currently being held in Helsinki. Most audience members, being hard-boiled scientists, did not believe they did. But Otaiku, whose work won the award for best clinical...

Gastrointestinal

Regeneron discloses new 17-β-HSD-13 inhibitors
Patents
Regeneron Pharmaceuticals Inc. has patented new 17-β-hydroxysteroid dehydrogenase 13 (HSD17B13; 17-β-HSD-13) inhibitors reported to be useful for the treatment of liver diseases.
Seabelife’s SBL-01 designated orphan drug in EU for acute liver failure
Regulatory
Seabelife SAS’s drug candidate SBL-01 has been awarded European orphan drug designation by the EMA for the treatment of acute liver failure.
Roche discovers new CCR6 antagonists
Patents
Researchers at F. Hoffmann-La Roche Ltd. and Hoffmann-La Roche Inc. have described C-C chemokine receptor type 6 (CCR6) antagonists reported to be useful for the treatment of asthma, psoriasis, Crohn’s disease, ulcerative colitis, multiple...
Microbiotica entering clinic with live bacterial therapeutics
Cancer
Microbiotica Ltd. is poised to advance two of its microbiome-derived products into the clinic after securing regulatory approval and fresh finance. The first live bacterial therapeutic, MB-097, will be tested in combination with Keytruda...
Hemoshear Therapeutics patents NTCP inhibitors for treatment of cholestasis
Patents
Hemoshear Therapeutics Inc. has identified new 3-((1,1-dioxido-2,3,4,5-tetrahydrobenzo[f][1,2,5]thiadiazepin-8-yl)oxy)-2-fluoroacrylic acid derivatives acting as sodium-bile acid cotransporter (SLC10A1; NTCP) inhibitors.
SOX7 plays key role in liver fibrosis by regulating hepatic stellate cell activation
The activation of hepatic stellate cells (HSCs) is a key process in the pathogenesis of liver fibrosis, but the molecular mechanisms behind it are not fully understood. By combining the analysis of differentially expressed gene screening of HSC...

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